| Title |
SMS regulates the expression and function of P-gp and MRP2 in Caco-2 cells
|
|---|---|
| Published in |
Cell Biology and Toxicology, July 2016
|
| DOI | 10.1007/s10565-016-9348-7 |
| Pubmed ID | |
| Authors |
Guiying Jin, Yang Li, Yuwen Zhu, Lisha Du, Junkai Yan, Qing Yang |
| Abstract |
Sphingomyelin synthase (SMS) has two isoforms of SMS1 and SMS2, the last enzyme involved in the biosynthesis of sphingomyelin (SM), and has impact on the expression of membrane proteins. In the present study, we explored the potential effects of SMS on drug transporters, a special family of membrane proteins in human intestinal epithelial Caco-2 cells. The specific knockdown of SMS1 or SMS2 with siRNA in Caco-2 cells substantially decreased the expression and function of P-glycoprotein (P-gp) and multidrug resistance protein 2 (MRP2) rather than other drug transporters MRP1, MRP3, PEPT1, OATP2B1, and BCRP. In the SMS1 stable overexpressed Caco-2 cell line, the expression levels of P-gp and MRP2 and transcription factor pregnane X receptor (PXR) were upregulated and the phosphorylation levels of signaling pathways janus protein tyrosine kinase 2 (JAK-2) and extracellular signal-regulated kinases (ERK) were also evidently increased; however, the upregulated mRNA expression levels of PXR, P-gp, and MRP2 were diminished by inhibiting the phosphorylation of ERK and JAK-2. Furthermore, the SMS1 overexpression in Caco-2 cells altered the expression levels of ERM proteins ezrin and moesin, which are closely connected to the function of drug transporters. In conclusion, we herein demonstrate for the first time that in Caco-2 cells SMS regulates the expression and function of drug transporters P-gp and MRP2, and their regulator PXR is mediated by phosphorylated ERK and JAK-2 signaling pathways. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Science communicators (journalists, bloggers, editors) | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 12 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 12 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 4 | 33% |
| Student > Ph. D. Student | 1 | 8% |
| Student > Postgraduate | 1 | 8% |
| Unknown | 6 | 50% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 3 | 25% |
| Agricultural and Biological Sciences | 2 | 17% |
| Medicine and Dentistry | 1 | 8% |
| Engineering | 1 | 8% |
| Unknown | 5 | 42% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 03 October 2016.
All research outputs
#15,385,802
of 22,890,496 outputs
Outputs from Cell Biology and Toxicology
#291
of 485 outputs
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#225,931
of 354,646 outputs
Outputs of similar age from Cell Biology and Toxicology
#10
of 17 outputs
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